Tapan Audhya, PhDNew York University, NY & Vitamin Diagnostics, NJ

Autism One 2009 Conference

Chicago, IL.

May, 2009

Unprovoked Seizures in Autistic Individuals

Seizure (Sudden, Abnormal electrical activity in brain)

Partial seizure (Focal, sensory or petit mal)(one part of brain; particularly the site which directs “flight” response; conscious; either tonic or clonic)

Generalized seizure

(Both site of brain)

Unconscious; Both tonic and clonic

Simple

(No loss of consciousness)Complex

Epilepsy – a recurrent seizure

Non-epileptic Seizure – Similar to epileptic.

Seizure but not caused by electrical disruption of cerebral cortex. Classified as 1) physiologic or 2) psychogenic

Nutritional Status of Autistic Nutritional Status of Autistic Children with SeizureChildren with Seizure

Age Group

4 -16 years ; N = 89 (Boys - 66, Girls – 23)

Repetitive Epileptic Seizure

1-7.2 min (mean – 4.0 min)

3 - 4 times a day

ICD-9 → 345.4;345.9;343.4;299.0

Epileptic Seizure was confirmed by EEG on29 boys and 5 girls

17 children had spinal tap for unrelated reason

Vitamin B1 in Plasma

32 low, 57 normal

Vitamin B6 in Plasma

30 low, 40 high, 44 low in P-5-P

Biotin in Plasma

23 low, 43 normal

These children were also hypoglycemic

Folic Acid in Plasma

Low only in those children who take anticonvulsant medication. 11 children had problem with impaired transport of folate across the BBB. 8/14 low in CSF

Vitamin E in Plasma

45 low, 2 high, 42 normal

Vitamin D in Plasma

27 low in D3;

(all of them had anticonvulsant medication)

Minerals

Magnesium

39 low in plasma

19 low in RBC

10 low in WBC

10/17 low in CSF

Selenium

8/17 low in CSF

20 low in Plasma

Manganese

32 low in plasma & RBC

Calcium

10/17 high in CSF

16 low in Plasma

5 high in RBC

Vitamins & Minerals

Protein & Amino AcidsProtein & Amino Acids

ProlactinProlactin 199 amino acid, Hypothalamic peptide & controlled 199 amino acid, Hypothalamic peptide & controlled

by Dopamineby Dopamine21 boys and 3 girls had high plasma prolactin 21 boys and 3 girls had high plasma prolactin

(2 -3x the normal levels)(2 -3x the normal levels)11 boys & 3 girls had low Dopamine11 boys & 3 girls had low Dopamine

GlutamateGlutamate 14/17 high glutamate in CSF, 42 high in Plasma14/17 high glutamate in CSF, 42 high in Plasma

AspertateAspertate 14 high in Plasma & CSF14 high in Plasma & CSF

TaurineTaurine 10/17 low in CSF, 34 low in Plasma10/17 low in CSF, 34 low in Plasma

GABAGABA 13/17 low in CSF, 28 high in Plasma, 59 low in Plasma13/17 low in CSF, 28 high in Plasma, 59 low in Plasma

Synthesis of GABA and Synthesis of GABA and αα--KetoglutarateKetoglutarate

Glutamine → Glutamate

Decarboxylase GABA P-5-P

Transaminase

P-5-Pα-Ketoglutarate

Glutathione PeroxidaseGlutathione Peroxidase

26 low normal26 low normal

34 less than half the normal value34 less than half the normal value

H202

H20 + 02

Glutathione Peroxidase (GP)

GSH GSSGGP

GR

SOD

Free Radical Oxygen

Autism, Seizure & Neurotransmitters Autism, Seizure & Neurotransmitters (NT)(NT)

NTs are chemicals that transfer information from one neuron to another

NTs have two basic functions

• Inform receiving neuron to “Fire” Excitatory

• Inform receiving neuron to stop “Firing” Inhibitory

These actions of NTs depend on a class of proteins which is known as receptors.

These receptors initiate the activity after receiving the NTs.

GABA, for example, binds to receptors which are inhibitory.

Most anti anxiety medications increase GABA transmission More GABA receptor activation Shut down the CNS Relaxation

GABA Receptor

GABAergic system in cerebellum and limbic structure in affected in autism. Inhibition of this system is suppressed by

1. Impairment of GABA-receptor

2. Antagonism of GABAergic neurons bearing receptors sensitive to glutamate analog NMDA.

Example:

Pathology relating to GABA receptors and suspected etiologies of autism

Excessive glutamate activation of non-NMDA glutamate receptor – Pathology observed in Autism

GABA Receptor submit Genes in AutismGABA Receptor submit Genes in AutismChromosomeChromosome GABA-receptor GABA-receptor

Subunit GeneSubunit Gene4p124p12 GABRG1GABRG1

-A2-A2

-A4-A4

-B1 -B1

5q345q34 -B2-B2

-A6-A6

-A1-A1

-G2-G2

-P-P

6q156q15 -R1-R1

-R2-R2

15q1215q12 -A5-A5

-B3-B3

-G3-G3

Only GABR A4 is involved in the etiology of autism and gene – gene interaction between GABR A4 and GABR B1

GABAGABAAA Receptor Receptor

GABAGABAAA Receptor Receptor

Controlling Seizures by Nutritional ApproachControlling Seizures by Nutritional ApproachKetogenic Diet : A diet high in fats, low in protein and carbohydrate.

Fat: (carb + protein) = 4:1

However, never make too low carb (Hypoglycemia) Medium chain Triglycerides (MCT) are more ketogenic.

TaurineTaurine 500 mg/day; 500 mg/day; divided in divided in

3 batches 3 batches

Vit – BVit – B11 20 mg/day 20 mg/day

Folic AcidFolic Acid 400 mcg/day 400 mcg/day Vit – BVit – B1212 200 mcg/day 200 mcg/day

Vit BVit B66 20 mg/kg Body wt. 20 mg/kg Body wt. Mg Mg 400 mg/day 400 mg/day

Mn Mn 5 mg/day 5 mg/day ZnZn 20 mg/day 20 mg/day

DMGDMG 100 mg/day 100 mg/day SeSe 100 mcg/day 100 mcg/day

L-CarnitineL-Carnitine 100 mg/day 100 mg/day Vit. E (natural)Vit. E (natural) 100 mg/day 100 mg/day

L-carnosineL-carnosine 250 mg/2 x day 250 mg/2 x day